Euploid miscarriage is associated with elevated serum C-reactive protein levels in infertile women: a pilot study

Abstract

Purpose Increased serum C-protein (CRP) levels reduce fecundity in healthy eumenorrheic women with 1-2 pregnancy losses. Subclinical systemic inflammation may impede maternal immune tolerance toward the fetal semi-allograft, compromising implantation and early embryonic development. Some miscarriages with normal karyotypes could, therefore, be caused by inflammation. Whether pre-pregnancy CRP relates to karyotypes of spontaneously aborted products of conception (POCs) was investigated. Methods A study cohort of 100 infertile women with missed abortions who underwent vacuum aspirations followed by cytogenetic analysis of their products of conception tissue was evaluated at an academically affiliated fertility center. Since a normal female fetus cannot be differentiated from maternal cell contamination (MCC) in conventional chromosomal analyses, POC testing was performed by chromosomal microarray analysis. MCC cases and incomplete data were excluded. Associations of elevated CRP with first trimester pregnancy loss in the presence of a normal fetal karyotype were investigated. Results Mean patients' age was 39.9 ± 5.8 years; they demonstrated a BMI of 23.9 ± 4.6 kg/m 2 and antiMullerian hormone (AMH) of 1.7 ± 2.4 ng/mL; 21.3% were parous, 19.1% reported no prior pregnancy losses, 36.2% 1-2 and 6.4% ≥ 3 losses. Karyotypes were normal in 34% and abnormal in 66%. Adjusted for BMI, women with elevated CRP were more likely to experience euploid pregnancy loss (p = 0.03). This relationship persisted when controlled for female age and AMH. Conclusions Women with elevated CRP levels were more likely to experience first trimester miscarriage with normal fetal karyotype. This relationship suggests an association between subclinical inflammation and miscarriage.

Does recurrent pregnancy loss have an inflammatory background?

“…In addition, they stated that some CRP gene variants increase the risk of recurrent pregnancy loss without causing an increase in CRP levels. In a recent retrospective study by Weghofer et al (23), preconceptional CRP values and genetic examination results of conception material of 100 infertile patients with missed abortion were evaluated. CRP values of individuals with euploid material were higher than those with aneuploid material.…”

Inflammation and Conception in a Prospective Time-to-Pregnancy Cohort

“…12,13,14 Higher serum CRP levels were reported among fertility treatment patients with unsuccessful intrauterine insemination cycles 15 or euploid pregnancy loss. 16 Circulating CRP levels were higher in women with unexplained infertility compared with fertile women and also higher in women with diminished ovarian reserve compared with women with normal ovarian reserve. Most of these studies are cross-sectional and do not directly examine the association of CRP on the probability of conceiving.…”

High-sensitivity C-reactive protein levels and pregnancy outcomes in women with unexplained infertility after ovarian stimulation with intrauterine insemination in a multicenter trial

“…Chromosomal microarray testing was performed on products of conception retrieved after dilation and curettage and was performed in patients undergoing fertility treatment for diminished ovarian reserve, male factor infertility, tubal factor infertility, polycystic ovarian syndrome, and endometriosis. They found that patients with hs-CRP levels ≥0.75 mg/L were more likely to have a euploid miscarriage as opposed to an aneuploid loss (odds ratio [OR], 5.5; 95% CI, 1.2–25.2, P =.03) ( 29 ). The greater proportion of euploid loss in the group with high levels of hs-CRP suggests that other potential factors, such as immune-mediated or inflammatory factors, may contribute to early pregnancy loss.…”